Atta Ur Rahman

Microbial transformation of 17α-ethynyl- and 17α-ethylsteroids, and tyrosinase inhibitory activity of transformed products

Abstract The microbial transformation of the 17α-ethynyl-17β-hydroxyandrost-4-en-3-one (1) (ethisterone) and 17α-ethyl-17β-hydroxyandrost-4-en-3-one (2) by the fungi Cephalosporium aphidicola and Cunninghamella elegans were investigated. Incubation of compound 1 with C. aphidicola afforded oxidized derivative, 17α-ethynyl-17β-hydroxyandrosta-1,4-dien-3-one (3), while with C. elegans afforded a new hydroxy derivative, 17α-ethynyl-11α,17β-dihydroxyandrost-4-en-3-one (4). On the other hand, the incubation of compound 2 with the fungus C. aphidicola afforded 17α-ethyl-17β-hydroxyandrosta-1,4-dien-3-one (5). Two new hydroxylated derivatives, 17α-ethyl-11α,17β-dihydroxyandrost-4-en-3-one (6) and 17α-ethyl-6α,17β-dihydroxy-5α-androstan-3-one (7) were obtained from the incubation of compound 2 with C. elegans. Compounds 1–6 exhibited tyrosinase inhibitory activity, with compound 6 being the most potent member (IC50xa0=xa01.72xa0μM).

New natural cholinesterase inhibiting and calcium channel blocking quinoline alkaloids

During this study, one new coumarin; 7-O-β-D-glucopyranoside-2H-1-benzopyran-2-one (1) and three quinoline alkaloids; 3-hydroxy, 2, 2, 6-trimethyl–3, 4, 5, 6-tetrahydro-2H-pyrano[3,2-c] quinoline 5-one (2), ribalinine (3) and methyl isoplatydesmine (4) were isolated from the aerial parts of Skimmia laureola and their structures established by spectroscopic studies. Compounds 2-4 were found to be linear mixed type inhibitors of acetylcholinesterase (Ki = 110.0, 30.0 and 30.0 μM, respectively). Compounds 2 and 3 were also found to be linear mixed type inhibitors of butyrylcholinesterase, while compound 4 was a noncompetitive inhibitor of the enzyme (Ki = 90.0, 70.0 and 19.0 μM, respectively). The inhibition of acetyl- and butyryl-cholinesterase enzymes persists as the most promising therapeutic strategy for activating the impaired cholinergic functions in Alzheimers disease and related dementias. Compound 4 also showed dose-dependent spasmolytic activity in the isolated rabbit jejunum intestinal preparation by relaxing the spontaneous (EC50 = 0.1 mg/mL) and K+-induced contractions (EC50 = 0.4 mg/mL), suggesting that the spasmolytic effect of compound 4 is mediated through the blockade of voltage-dependent Ca2 + channels.

Fungal transformation of cedryl acetate and α-glucosidase inhibition assay, quantum mechanical calculations and molecular docking studies of its metabolites.

The fungal transformation of cedryl acetate (1) was investigated for the first time by using Cunninghamella elegans. The metabolites obtained include, 10β-hydroxycedryl acetate (3), 2α, 10β-dihydroxycedryl acetate (4), 2α-hydroxy-10-oxocedryl acetate (5), 3α,10β-dihydroxycedryl acetate (6), 3α,10α-dihydroxycedryl acetate (7), 10β,14α-dihydroxy cedryl acetate (8), 3β,10β-cedr-8(15)-ene-3,10-diol (9), and 3α,8β,10β -dihydroxycedrol (10). Compounds 1, 2, and 4 showed α-glucosidase inhibitory activity, whereby 1 was more potent than the standard inhibitor, acarbose, against yeast α-glucosidase. Detailed docking studies were performed on all experimentally active compounds to study the molecular interaction and binding mode in the active site of the modeled yeast α-glucosidase and human intestinal maltase glucoamylase. All active ligands were found to have greater binding affinity with the yeast α-glucosidase as compared to that of human homolog, the intestinal maltase, by an average value of approximately -1.4 kcal/mol, however, no significant difference was observed in the case of pancreatic amylase.

Successful computer guided planned synthesis of (4R)-thiazolidine carboxylic acid and its 2-substituted analogues as urease inhibitors

By using internal combinatorial library we were able to identify (4R)-thiazolidines carboxylic acid and its 2-substituted analogs as active inhibitors of urease. Molecular modeling and virtual screening were utilized to find out potential compounds. Computational techniques were employed at database of 90,000 ligands and selected the structure representing the low energy conformations, Grid and FlexX docking algorithms were used and the top binding ligands were synthesized and screened in wet-lab.

Microbial Transformations of Testosterone

Abstract Microbial transformation of testosterone (17β-hydroxyandrost-4-en-3-one) (1) by Curvularia lunata and Pleurotus oestreatus yielded 17-dehydrotestosterone (androst-4-ene-3,17-dione) (2) and 15α-hydroxytestosterone (15α, 17β-dihydroxyandrost-4-en-3- one) (3), respectively.

New natural products from medicinal plants of Pakistan

A number of new natural products have been isolated from medicinal plants of Pakistan. Some of them have exhibited antifungal activities. Structure of those compounds were determined with the help of spectroscopic studies.

New antibacterial steroidal alkaloids from Sarcococca brevifolia

Abstract Three new steroidal alkaloids, epipachysamine-E-5-ene-4-one (1), N b-demethylepipachysamine-E-5-ene-4-one (2) and iso-N-formylchonemorphine (3) have been isolated from Sarcococca brevifolia. Structures of these compounds were determined by spectroscopic studies. Compounds 1 and 3 exhibited strong antibacterial activity against Bacillus cereus, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, Corynebacterium diphtheriae and Pseudomonas aeruginosa.

MICROBIAL TRANSFORMATION OF SOME BIOACTIVE NATURAL PRODUCTS

Abstract The microbial transformation of vindoline (1) by Aspergillus niger, Fusarium lini and F. monolinum afforded 17-deacetylvindoline (2) as the sole metabolic product, whereas α-santonin (3) was regiospecifically reduced to 1,2-dihydro-α-santonin (4) by Aspergillus niger.

Phytochemical Studies On Skimmia Laureola

Abstract 3-Oxo-lanosta-20-25-diene-3-one (1), a new lanostan-type triterpene along with a new alkaloid methylisoplatydesmine (2) have been isolated from the aerial parts of Skimmia laureola. the structures of these compounds were determined by spectral studies.

Artonin I inhibits multidrug resistance in Staphylococcus aureus and potentiates the action of inactive antibiotics in vitro.

The emergence of multidrug‐resistant (MDR) Staphylococcus aureus is a challenge for the treatment of infections. We report here the antimicrobial activity of artonin I against MDR Staph. aureus, its mechanism of reversal of resistance and synergistic effects by combinational therapy.